Good Clinical Practice GCP Clinical Trial Registries The

Good Clinical Practice (GCP) & Clinical Trial Registries The Fifth Annual Pharmaceutical Regulatory and Compliance Congress and Best Practice Forum November 14 -17, 2004 Kate Maloney, RN, MS, CPHQ Manager, Pharmaceutical Industry Advisory Services pwc

GCP, Trial Registries & More Good Clinical Practice 2 Pricewaterhouse. Coopers

Good Clinical Practice Guideline n o i t a l u g e R ICH GCP FDA GCP 3 Dir ec tiv e EU Directive Pricewaterhouse. Coopers

Good Clinical Practice ICH GCP Guideline Objective “To provide a unified standard for the European Union (EU), Japan, and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions” Source: pharmacos. eudra. org 4 Pricewaterhouse. Coopers

Good Clinical Practice FDA GCP vs. ICH GCP Ø The FDA maintains that ICH GCP guideline (E 6) is entirely consistent with the agency’s GCP regulations and clinical studies conducted under these guidelines meet the GCP standards acceptable to FDA. Ø Conventional wisdom … ICH GCP when doing studies for global NDA submission 5 Pricewaterhouse. Coopers

Good Clinical Practice European Union Clinical Trial Directive Ø Scope of legislation is much broader than strict GCP Ø Encompasses: Manufacture of investigational medicinal products Laboratory testing services 6 Pricewaterhouse. Coopers

Good Clinical Practice GCP Compliance Plan is essential Ø Appx. ¾ of cost of drug development is in clinical trial phase Ø Expanded globalization of studies Ø Diversity of organizations involved in any trial can: Be substantial Difficult to manage Expose sponsor to GCP compliance risk Ø Outsourcing to CROs R&D outsourcing expenditures rising at rate in excess of 14% per year 1 Accounted for 70% of market in 2003 – expected to grow to almost 80% by 20082 Sources: Pink Sheet, 2003; 65(50): 30 / 2003 report by Kalorama Information 7 Pricewaterhouse. Coopers

Clinical Trial Cycle 1. Sponsor + PI + Institution/CRO contact: Proposal & Budget Prepared 8. Dossier prepared for NDA submission 2. IRB approves study and informed consent form, Scientific & Regulatory Reviews approved 1 8 2 7. Trial ends: All data submitted to Sponsor 6. Adverse Events Reporting Enrollment Continues Continuing IRB Reviews Continuous Improvement of Medical and Business Practices 7 6 5 4 3 3. Contract Accepted by all parties - study initiated 4. Patients Enrolled by Proper Selection Criteria/ Informed Consent Used, Trial Begins 5. Data Collected for Sponsor as patients receive treatment 8 Pricewaterhouse. Coopers

Good Clinical Practice Regulators are focusing on “research compliance” Ø The collection of evolving government requirements • Focus of complex rules and penalties from various federal and international agencies. • Can torpedo the reputation of even the most prestigious companies. 9 Pricewaterhouse. Coopers

Good Clinical Practice Ø Non-compliance exposes corporations to heightened risks • • 10 Hefty fines Significant trial delays Endangered patient safety Wasted resources Lost profit margins Embarrassment Potential litigation Reputational damage Pricewaterhouse. Coopers

Good Clinical Practice FDA gearing up for: Ø More Frequent Ø Intensive Ø Unannounced Inspections Sponsor operational changes will undoubtedly have an effect Ø Patient Recruitment Ø Electronic Data Collection & Management Ø Outsourced Clinical Activities Ø Trial results disclosure EU Directive enforcement will have direct impact 11 Pricewaterhouse. Coopers

Good Clinical Practice Nearly 4, 000 clinical trials, Phase I, II, or III, are taking place worldwide Source: Parexel’s Pharma R&D Statistical Sourcebook 04/05 12 Pricewaterhouse. Coopers

Good Clinical Practice Clinical trials in developing nations Ø “Ascending Markets” Eastern Europe • Aligning with European practices, including ICH-GCP India • Lags in GCP experience • Regulatory changes underway to promote GCP training Asia • GCP practices and understanding “poor to fair” • Sponsors & CROs investing in GCP training Latin America • Needs regulatory reform Ø 20% - 30% of trials conducted in these markets Source: Applied Clinical Trials, June 04 13 Pricewaterhouse. Coopers

Good Clinical Practice FDA priorities for the coming year Ø Focus on high priority safety areas • Adverse Events (AE) Improve efficiency & effectiveness of AE reporting system Goal: Develop common reporting system used as single point of entry for patients, consumers, & health care providers to report all AEs and product problems FDA Adverse Event Reporting System (FEARS) Source: HHH/FDA Progress and Priorities 2004: Protecting and Advancing America’s Health 14 Pricewaterhouse. Coopers

Good Clinical Practice • Safety Reporting Codify expectations for timely acquisition, evaluation, & submission of relevant safety information Ø Clinical Trials Registry • Clinical. Trials. gov FDA checking compliance rates through April 03* Industry non-compliance has been on-going concern Survey of cancer INDs found only 47% listed Source: FDA Pink Sheet V 66(26)p 30 15 Pricewaterhouse. Coopers

GCP, Trial Registries & More Clinical Trial Registry 16 Pricewaterhouse. Coopers

Clinical Trial Registry 17 Pricewaterhouse. Coopers

Clinical Trial Registry In the United States Registry Open clinical studies for serious or life-threatening diseases posted in Clinical. Trials. gov 18 Pricewaterhouse. Coopers

Clinical Trial Registry 19 19 Pricewaterhouse. Coopers

Clinical Trial Registry What should be in the registry? At least this “barebones info” Disease Investigational New Drug Pre-clinical information Location of studies Results of all studies done Contact information 20 Pricewaterhouse. Coopers

Clinical Trial Registry In the European Union Registry All new trials must have a Eudra. CT number for tracking Adverse Events Reporting Eudra. Vigilance Module (linked to the Eudra. CT database) 21 Pwc Pricewaterhouse. Coopers

Eudra. CT Database Information included: • Title of trial • Sites • Sponsor identity • Dosing and duration • Details & hx. of IND being tested/used as comparator • Population of trial subjects and details (including pharmaceutical form, route of adm. , all strengths used, provenance of active substance) • Principal and coordinating investigators • Details of medical condition on which trial is focused • Central technical facilities • Main and secondary objectives • Duties subcontracted • Principal inclusion and exclusion criteria • Trial monitoring facilities • Primary endpoints • Ethics committee details • Scope and phase of trial • Protocol details • Design of trial Will not contain individual personal information relating to clinical trial subjects (provision of GCP) 22 Pricewaterhouse. Coopers

GCP, Trial Registries & More Recent Update 23 Pricewaterhouse. Coopers

and more … Pharmacogenomics Ø The study of variability in drug handling or response due to hereditary factors in different populations. ØIf an argument can be made for genotyping subjects prior to enrollment in a clinical trial to reduce screening failures, the FDA may expect sponsors of clinical trials to incorporate pharmacogenetics testing in protocols Source: Applied Clinical Trials. “The Future of Clinical Diagnostics. Oct 04 24 Pricewaterhouse. Coopers

and more … Computerized Systems in Clinical Trials Ø FDA statement “We recommend that each study protocol identify at which steps a computerized system will be used to create, modify, maintain, archive, retrieve, or transmit data. ” Source: FDA Draft Guidance on Computerized Systems Used in Clinical Trials. Sept 04 25 Pricewaterhouse. Coopers

Conclusion Ø Assess global clinical compliance risk Ø Deploy resources to promote and achieve GCP Ø Address issues preventing company from meeting compliance objectives 26 Pricewaterhouse. Coopers

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